Targeted at learning about the pathogenesis of inflammatory eye diseases grouped under the term uveitis, this project in FY 1991 focused mainly on two procedures aimed at modulation of experimental autoimmune uveoretinitis (EAU), an animal ocular disease considered to be a model for uveitis in man. In one procedure, we inhibited EAU in rats by injecting uveitogenic peptides intravenously, in aqueous solution. Both immunodominant and nondominant peptides could cause this state of anergy, but only the dominant peptide could inhibit EAU induced by the whole protein (interphotoreceptor retinoid-binding protein), and its minimal dose for the anergy induction was much smaller than that of the nondominant peptide. The anergy induced by this procedure was highly specific: Analogs of the uveitogenic peptide in which one residue was substituted with alanine did not induce anergy against the native peptide. A state of anergy was also induced in vitro, by a newly developed procedure in which lymphocytes are exposed to the peptides in the absence of antigen-presenting cells. The second procedure we tested for its possible modulatory effect on EAU is the vaccination with a T cell receptor (TCR) Vbeta 8.2 peptide. This peptide is derived from the sequence of the TCR element which is selectively used by lymphocytes that induce autoimmune diseases, including EAU. Vaccination with this peptide was reported to prevent the development of experimental allergic encephalomyelitis (EAE) completely. Despite adherence to the published procedure, however, we could not reproduce its reported striking effect on EAE and observed inconsistent effects on EAU. Moreover, our finding of a partial and variable effect of the vaccination has recently been confirmed by other laboratories. The Vbeta 8.2 peptide is a component of a self protein present on lymphocytes of the vaccinated rats. It is notable that these rats responded vigorously against this autologous peptide. The finding thus sheds new light on the issue of immunogenicity of autologous antigens. Another topic investigated in FY 1991 is stimulation of lymphocytes by staphylococcal enterotoxin B (SEB). This bacterial product, a potent mitogen, stimulates proliferation by lymphocytes of various species, including the rat. However, stimulation with SEB was found to have minimal or no effect on the uveitogenic activity of rat lymphocytes sensitized against uveitogenic antigens. This finding shows, again, the dissociation between lymphocytes' stimulation for proliferation and for disease induction.